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Biomedical subjects

J K Farrar

Publications and source records attributed to J K Farrar.

At least 19 recordsLinked to original sources
PubMed1992

Methylparaben and propylparaben do not alter cerebral blood flow in humans.

In vitro studies suggest that the preservatives methylparaben and propylparaben included in some multidose vials of succinylcholine are the cerebral vasodilators responsible for the increases in intracranial pressure (ICP) documented after succinylcholine administration. To test this hypothesis, we measured cerebral blood flow (CBF) and cerebral blood flow velocity (CBFV) with inhaled 133Xenon and transcranial Doppler respectively in healthy humans before and after the intravenous administration of methylparaben and propylparaben. We found no change in either CBF or CBFV after the paraben injections and therefore conclude that it is unlikely that the rise in ICP seen with succinylcholine is caused by cerebral arterial vasodilatation from the preservatives methylparaben and propylparaben.

Cerebrovascular Circulation↗
PubMed1992

The responsiveness of cerebral blood flow to changes in arterial carbon dioxide is maintained during propofol-nitrous oxide anesthesia in humans.

Because it is common to manipulate PaCO2 during neurosurgery, it is essential to characterize the relationship between cerebral blood flow (CBF) and changes in PaCO2. The purpose of this study was to investigate the effects of propofol-N2O anesthesia on the CBF response to changes in PaCO2 in healthy subjects. In seven patients, anesthesia was induced with propofol 2.0-2.5 mg/kg and then maintained with a propofol infusion of 12 mg.kg-1.h-1 for 10 min and then 9 mg.kg-1.h-1 for 10 min and then was reduced to 3-6 mg.kg-1.h-1 for the remainder of the study. The subjects' lungs were ventilated with N2O in O2 (FIO2 0.3) to the end-tidal CO2 present before anesthesia, and then CBF was measured using intravenous 133Xe and ten scintillation counters, five over each cerebral hemisphere. ETCO2 then was increased to 50 mmHg and CBF measurement repeated; ETCO2 then was reduced to 30 mmHg and CBF measurement repeated. Concurrent with each CBF measurement, arterial blood was sampled for PaCO2 and hemoglobin measurement. CBF at normocapnia (PaCO2 42 +/- 2 mmHg) was 33 +/- 7 ml.100 g-1.min-1, which increased to 58 +/- 10 ml.100 g-1.min-1 and decreased to 19 +/- 4 ml.100 g-1.min-1 on increasing PaCO2 (53 +/- 4 mmHg) and decreasing PaCO2 (31 +/- 2 mmHg), respectively. Both the PaCO2 and CBF values were statistically different from those measured at any other time (CBF P less than 0.002, PaCO2 P less than 0.001). The slope of CBF versus PaCO2 was 1.56 ml.100 g-1.min-1.mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Autoregulation and the CO2 responsiveness of cerebral blood flow after cardiopulmonary bypass.

Cerebral blood flow (CBF) was measured by 133Xe clearance to determine whether there were any residual effects of cardiopulmonary bypass (CPB) on the CBF response to changes in arterial PCO2 or blood pressure in the early (3-8 hr) post-CPB period. During CPB, the nine patients studied were managed according to alpha-stat, temperature uncorrected, pH management. The mean +/- SD increase in CBF resulting from an increase in PaCO2 (1.35 +/- 0.5 ml.100 g-1.min-1.mmHg-1 PaCO2) was within the normal range, indicating appropriate CBF response to a change in PaCO2. There were no significant differences in CBF, being 25.7 ml.100 g-1.min-1 at a mean arterial blood pressure of 70 mmHg and 26.5 ml.100 g-1.min-1 at 110 mmHg, demonstrating intact cerebral autoregulation over this pressure range. We conclude that cerebral autoregulation and CO2 responsiveness are preserved in the immediate postoperative period after CPB using alpha-stat pH management.

Aged↗
PubMed1987

Cerebral autoregulation and flow/metabolism coupling during cardiopulmonary bypass: the influence of PaCO2.

Measurement of 133Xe clearance and effluent cerebral venous blood sampling were used in 38 patients to determine the effects of cardiopulmonary bypass, and of maintaining temperature corrected or noncorrected PaCO2 at 40 mm Hg on regulation of cerebral blood flow (CBF) and flow/metabolism coupling. After induction of anesthesia with diazepam and fentanyl, mean CBF was 25 ml X 100 g-1 X min-1 and cerebral oxygen consumption, 1.67 ml X 100 g-1 X min-1. Cerebral oxygen consumption during nonpulsatile cardiopulmonary bypass at 26 degrees C was reduced to 0.42 ml X 100 g-1 X min-1 in both groups. CBF was reduced to 14-15 ml X 100 g-1 X min-1 in the non-temperature-corrected group (n = 21), was independent of cerebral perfusion pressure over the range of 20-100 mm Hg, but correlated with cerebral oxygen consumption. In the temperature-corrected group (n = 17), CBF varied from 22 to 32 ml X 100 g-1 X min-1, and flow/metabolism coupling was not maintained (i.e., CBF and cerebral oxygen consumption varied independently). However, variation in CBF correlated significantly with cerebral perfusion pressure over the pressure range of 15-95 mm Hg. This study demonstrates a profound reduction in cerebral oxygen consumption during hypothermic nonpulsatile cardiopulmonary bypass. When a non-temperature-corrected PaCO2 of approximately 40 mm Hg was maintained, CBF was lower, and analysis of pooled data suggested that CBF regulation was better preserved, i.e., CBF was independent of pressure changes and dependent upon cerebral oxygen consumption.

Acid-Base Equilibrium↗
PubMed1987

Pharmacologic EEG suppression during cardiopulmonary bypass: cerebral hemodynamic and metabolic effects of thiopental or isoflurane during hypothermia and normothermia.

We have determined the effects of thiopental or isoflurane upon cerebral blood flow (CBF) and the cerebral metabolic rate for oxygen (CMRO2) when these agents are used in sufficient dose to attain a deep burst suppression pattern on the electroencephalogram (EEG) during hypothermic and normothermic cardiopulmonary bypass (CPB). Thirty-one patients undergoing coronary artery bypass graft surgery were anesthetized with fentanyl 0.1 mg X kg-1, and were randomly allocated to one of three groups: control (no further anesthetics during bypass and continuous EEG activity), thiopental treatment (EEG suppression), or isoflurane treatment (EEG suppression). Hypothermia (25-29 degrees C) was routinely induced at onset of nonpulsatile cardiopulmonary bypass. In the treatment groups, thiopental or isoflurane were used during bypass to achieve a deep burst suppression pattern. Cerebral blood flow and cerebral metabolic rate for oxygen were determined during hypothermia and upon rewarming to normothermia (37 degrees C). Pharmacologic EEG suppression with either isoflurane or thiopental was associated with lower cerebral metabolic rate than control values during both hypothermic and normothermic bypass. However, only thiopental-induced EEG suppression was associated with lower cerebral blood flow than control. Cerebral blood flow during isoflurane-induced EEG suppression was similar to control values in spite of the reduced cerebral metabolic rate.

Blood Gas Analysis↗
PubMed1985

Contribution of the inflow arteries to alterations in total cerebrovascular resistance in the rabbit.

The contribution made by the cerebral inflow arteries to total cerebrovascular resistance (CVR) and their importance in producing alterations in cerebral blood flow (CBF) (i.e., changes in CVR) were investigated. The arterial blood pressure at the circle of Willis was measured in 14 anesthetized rabbits via transorbital retrograde cannulation of the ophthalmic artery. CBF was measured in 21 rabbits under identical experimental conditions, using the hydrogen clearance technique. Inflow artery resistance was calculated from the measurements which were made at both normocapnia and hypercapnia throughout hemorrhagic hypotension. Under resting conditions, the inflow arteries made a relatively minor contribution to total CVR (7%). Hypercapnia resulted in a decrease in CVR and an increase in CBF; however, inflow artery resistance remained constant. Autoregulation and reductions in total CVR were observed as PP was reduced to 35 mm Hg. Inflow artery resistance remained constant at pressures greater than 45 mm Hg and increased slightly at PP less than 45 mm Hg. The relative contribution of inflow artery resistance to total CVR increased under the various conditions studied--increasing by a factor of 2 during hypercapnia, by a factor of 3 during hypotension, and by a factor of 4 during hypotension + hypercapnia. We concluded that the large inflow arteries do not participate in the autoregulatory or CO2 responses of the cerebrovasculature of the rabbit.

Animals↗
PubMed1985

[Effect of naloxone on focal cerebral ischemia in cats].

The effect of naloxone, opiate antagonist, was investigated on systemic arterial blood pressure(BP), cerebral blood flow (CBF), and cerebral oxygen consumption in the cat brain following occlusion of the middle cerebral artery(MCA). A total of 21 adult cats was studied under the anesthesia of alpha-chloralose (50 mg/kg). The left MCA was exposed and coagulated using transorbital approach under a operation microscope. Naloxone of 5 mg/kg was administrated intravenously within 30 minutes after MCA occlusion in early therapy group and 2.5 hours after the occlusion in delayed therapy group. Isotonic saline was administrated in the control group. The basal value of CBF in the intact animals was 54.0 +/- 5.9 (+/- SEM) ml/100g/min. Significant increases in mean BP of 13%, CBF of 12%, and CMRO2 of 16% were noted in the intact animals after naloxone administration. The CBF in MCA territory reduced to 24% after MCA occlusion and 85% in contralateral hemisphere. MCA occlusion had no significant effect on either mean BP or the difference in oxygen concentration between arterial and superior sagittal sinus blood. Naloxone increased these reduced CBF and mean BP significantly, but increase in oxygen consumption was not significant. There was no difference between early therapy group and delayed therapy group in pathological study. The effect of naloxone was temporary. Therapy of repeated or continuous naloxone administration appears to be effective during temporary focal cerebral ischemia.

Animals↗
PubMed1984

Pial vessel caliber and cerebral blood flow during hemorrhage and hypercapnia in the rabbit.

We examined the relationship between cerebral blood flow (CBF) and pial vessel caliber responses to graded hemorrhagic hypotension at both normocapnia and hypercapnia in 31 anesthetized rabbits. Changes in CBF (hydrogen clearance) and pial arteriolar diameter (image splitting) were predictably related at all perfusion pressures (PP). Three autoregulatory regions were identified. 1) At PP greater than 65 mmHg, autoregulation was complete as CBF and the CBF response to hypercapnia remained at control levels. The pial vessels dilated progressively, and their response to hypercapnia increased. 2) At PP between 65 and 35 mmHg autoregulation continued but was incomplete. CBF decreased proportionately less than the corresponding reductions in PP due to continued pial vascular dilatation. Both the CBF and pial vessel responses to hypercapnia diminished. 3) At PP less than 35 mmHg, autoregulation was abolished. Pial arteriolar caliber and CBF decreased pressure passively, and there were no responses to hypercapnia. A comparison of changes in pial vascular resistance and total precapillary resistance indicated that the responses of pial vessels (particularly those less than 50 micron) paralleled the responses of the intraparenchymal arterioles.

Animals↗
PubMed1983

The influence of systemic arterial pressure and intracranial pressure on the development of cerebral vasogenic edema.

The influence of intracranial pressure (ICP), systemic arterial pressure (SAP), and cerebral perfusion pressure (CPP) upon the development of vasogenic cerebral edema is largely unknown. To study their relationship, the authors have produced an osmotic disruption of the blood-brain barrier unilaterally in rabbits by injecting 1 cc/kg of 2M NaCl into the left internal carotid artery. The amount of vasogenic edema produced was assessed by quantitation of the extravasation of Evans blue dye into the area of maximum blood-brain barrier breakdown by means of optical densitometry following formamide extraction. The ICP was measured using a cisterna magna catheter into which mock cerebrospinal fluid could be infused at a predetermined pressure. The SAP was controlled by exsanguination from a femoral artery catheter. In 18 animals in which blood pressure was not controlled, no significant relationship between the ICP and the degree of Evans blue dye extravasation was noted. In these animals, however, a direct relationship between CPP (defined as mean arterial pressure minus mean ICP) and extravasation of Evans blue dye was found (correlation coefficient 0.630; p less than 0.001). When ICP was held constant at 0 to 5 mm Hg in another group of 16 animals and different levels of blood pressure were produced by exsanguination, a significant direct relationship between extravasation of Evans blue dye and the SAP was found (correlation coefficient 0.786; p less than 0.001). In a third group of 20 animals, the blood pressure was held constant at 90 to 100 mm Hg and the ICP was varied between 0 and 75 mm Hg. There was a highly significant result indicating increasing Evans blue dye extravasation with lower levels of ICP (p less than 0.001). Cerebral blood flow determinations by the hydrogen clearance method indicated loss of autoregulation in all animals in the areas of brain injured by intracarotid hypertonic saline. These results indicate that high SAP and low ICP (that is, a large CPP) promote Evans blue dye extravasation in this model of blood-brain barrier disruption. This finding has implications for the management of patients with vasogenic edema.

Animals↗
PubMed1982

Monitoring the safe levels of hypotension. IV. The role of cerebral blood flow studies.

It is now possible to monitor CBF during aneurysm surgery using a relatively simple, noninvasive technique. This should improve the safety of the use of controlled hypotension and may well identify those patients requiring more aggressive postoperative treatment. Intraoperative CBF monitoring will also provide valuable information concerning the cerebrovascular effects of the various hypotensive agents used, as well as the pathophysiology of CBF regulation.

Brain Diseases↗
PubMed1981

Effects of profound hypotension on cerebral blood flow during surgery for intracranial aneurysms.

The progression of changes in cerebral blood flow (CBF) and neurological status were measured in 12 patients in whom profound hypotension (mean arterial blood pressure (MABP): 30 to 40 mm Hg) was used during intracranial aneurysm surgery. Nine patients (Group I) showed autoregulation of CBF to an MABP of 40 to 50 mm Hg during surgery. None of these patients had arterial spasm preoperatively. Postoperatively, mild flow disturbances were noted at the site of retraction. Three Group I patients developed arterial spasm postoperatively, but there was no associated neurological deterioration. The remaining three patients (Group II) had impaired autoregulation during surgery, and CBF decreased by 35% to 65% at an MABP of 50 mm Hg. Two of these patients had angiography immediately before surgery, and both showed moderate to severe arterial spasm. Relatively severe flow disturbances were noted postoperatively at the site of retraction, and two patients developed ischemic deficits of late onset. Brain retractor pressure and the degree and duration of hypotension were equivalent in the two patient groups. There was no correlation between intraoperative reductions in CBF (to as low as 20 ml/100 gm/min in the unretracted hemisphere) and immediate postoperative neurological deficits. The use of halothane and mannitol and the relatively short duration of the flow reductions were suggested as factors contributing to the protection from ischemia that was observed. Arterial spasm was found to produce hemodynamic instability and reduced CBF, although neurological status was unaffected in the majority of patients. Patients with impaired autoregulation during surgery were at increased risk of delayed ischemic complications postoperatively, and showed characteristic flow disturbances at all three stages of their clinical course.

Angiography↗
PubMed1977

Vascular reactivity in the primate brain after acute cryogenic injury.

The effects of an acute cryogenic injury on cerebral flow (CBF) and cerebral vascular reactivity were studied in 12 anaesthetised, ventilated baboons. Autoregulation, defined in this study as intact with a greater than 20% change in cerebrovascular resistance in response to a change in cerebral perfusion pressure, was tested before the lesion by arterial hypotension. Intact autoregulation was found in half the animals, but all animals showed an increase in CBF with hypercarbia. The cryogenic lesion was followed by a marked rise in intracranial pressure, and a fall in CBF which was only partly related to the status of autoregulation beforehand. After injury, arterial hypertension caused an increase in cerebrovascular resistance of more than 20% in half the animals. This response was not related to the presence of autoregulation before the lesion, and was accompanied by a greater impairment of the cerebrovascular response to carbon dioxide, more severe brain oedema, and lower cerebral oxygen consumption, than in the remaining baboons which had a pressure passive response to arterial hypertension. This study confirms that the failure of CBF to increase with arterial hypertension may indicate severe brain damage rather than intact physiological autoregulation.

Animals↗